外源性基质金属蛋白酶抑制剂GM6001对FDM形成的抑制作用  

Inhibitory effects of Galardin on the development of form-deprivation myopia of chick

作　　者：吴文灿[1] 刘双珍[2] 颜文韬[1] 王剑峰[2] 谭星平[2] 

机构地区：[1]温州医学院附属眼视光医院,325027 [2]中南大学湘雅医院眼科,长沙410078

出　　处：《眼科研究》2006年第4期397-401,共5页Chinese Ophthalmic Research

基　　金：湖南省科技厅社会发展基金资助(04SK3034-4)

摘　　要：目的研究非特异性基质金属蛋白酶(MMPs)抑制剂GM6001对小鸡形觉剥夺性近视眼(FDM)形成的影响。方法150只1d龄来亨雏鸡采用半透明塑料眼罩单眼遮盖制备FDM动物模型,同时每日球后注射不同剂量GM6001连续4d、14d。检测眼轴长度及屈光度,观察后极部巩膜组织病理学变化及检测MMP-2蛋白质、酶活性及其mRNA的表达。结果GM6001明显抑制遮盖4d眼FDM的形成,对遮盖14d眼仅部分抑制,对正常鸡无作用。GM6001干预后,遮盖14d眼后极部巩膜组织病理学改变与FDM相似,后极部巩膜MMP-2表达显著降低,而遮盖4d组均与正常小鸡眼相似。GM6001干预眼明胶酶谱图未检测到透亮带。GM6001对后极部巩膜MMP-2mRNA表达无影响。结论MMP-2活性增高为小鸡细胞外基质(ECM)后极部巩膜ECM重塑的关键因素之一。Objective To investigate the inhibitory effects of Galardin （GM6001）, a tissue inhibitor of matrix metalloproteinase （ MMP）, on the development of form-deprivation myopia （ FDM ）. Methods Animal model of FDM was established in 150 chicks through monocular occlusion with semi-translucent plastic goggle for 4 days or 14 days. Animal models were divided randomly into GM6001 group,PBS group and negative control group. 10,50 and 100 μmol/50 μl of Galardin was injected retroocularly in chicks of GM6001 group respectively ,and 50μl of PBS was used at the same way in PBS group and no any interference was applied in negative control group. The eyes from other 150 1-day-old chickens did not occluded as control groups. Axial length and refractive degree of experimental eyes were measured after 4 or 14 days. Pathologic changes of sclera tissue was examined using HE staining,and MMP-2 expression was evaluated using immunohistochemistry,and the expression of mRNA and enzyme activity of MMP-2 was detected by RT-PCR and gelatin enzymography ,separately. Results The increases of axial length and myopic refractive degree were suppressed by various concentration of Galardin in GM6001 4-day group compared with PBS and negative control group （P 〈0.01 ,P 〈0.01 ）. However,the inhibitory effect was indistinct in GM6001 14- day group. No significant effects of Galardin was found in normal control groups. A few membranes of ehondrocytes and cartilage vesicles showed positive dye both in normal non-deprived eyes and in GM6001 4-day group in comparison with FMD groups and FMD 14-day group. Levels of MMP-2 activity in FDM groups were much higher than in normal control groups,and these changes were more significant with the time increase of monocular deprivation. However,in groups treated with Galardin, there were no positive bands appeared on the map of gelatin enzymography. No effects of Galardin on MMP-2 mRNA expression were seen both in normal control group and in FDM groups. Conclusion Increase of MMP-2 enzyme acti

关 键 词：形觉剥夺性近视眼 GM6001 抑制作用 小鸡 

分 类 号：R965[医药卫生—药理学]